Project Abstract The goal of this R21 proposal is to develop a robust, minimally invasive wireless photometry system for in vivo calcium measures in freely moving behavior. To achieve this, a miniaturized, wireless, `injectable' photometry platform (~300 mm wide, ~100 mm thick and several mm long) that enables quantitative measurements of fluorescence stimulated using a high performance microscale inorganic light emitting diode (-ILED) and captured using a co-located, sensitive microscale inorganic photodetector (-IPD) is proposed. These devices directly address current limitations in measuring calcium transient activity within any environment and facilitate sensing of genetically defined neural networks in more ethologically relevant behaviors -- central goal of the BRAIN initiative and RFA-EY-16-001. These small-scale device components will mount on thin, flexible filaments with overall dimensions significantly smaller than fiber optic cables. The resulting systems will greatly reduce motion artifacts, due to their direct integration at targeted regions of the brain; when implemented using wireless schemes for power delivery and data communication, they will allow complete freedom of motion of awake, behaving animals, suitable for use in complex, three dimensional environments and in socially interacting communities. Preliminary data from using hard-wired versions of these technologies and separate demonstrations of wireless implantable platforms establish feasibility of the foundational concepts. This proposal is divided into following two aims: Specific Aim 1: To examine brain activity in real-time on awake, behaving animals using a platform of injectable -ILEDs and -IPDs, with a test case measuring the fear conditioning responses. The thin, flexible, lithographically defined photometry probes will be insert into targeted regions of the deep brain, such as the basolateral amygdala (BLA), including lateral, basal, and accessory basal nuclei using stereotactic positioning hardware and surgical procedures adopted from those used in previous wireless, injectable systems for optogenetics. Specific Aim 2: To develop wireless schemes for power delivery and data communication for these systems, with demonstrations in fear conditioning and social interaction. Further size reductions and purely wireless modes of operation will greatly enhance the technology and the opportunities in neuroscience studies. Behavior experiments including fear conditioning (outlined in Aim 1) and social interaction (known to evoke BLA activity) will serve to demonstrate and optimize the fully wireless capabilities.